1. Technical Field
The present invention is related to a method of culturing Bordetella pertussis (B. pertussis) on a large scale. More particularly, the present invention is related to a method of fermentation level cultivation of B. pertussis concurrently producing pertussis toxin.
2. State of the Art
Pertussis toxin is one of the various components produced by virulent B. pertussis, the microorganism that causes whooping cough. This toxin is a major protective antigen against whooping cough. Other components of interest produced by B. pertussis are filamentous hemagglutinin, heat labile toxin, adenylate cyclase and the like which may also play important role as protective antigens. Large scale production of these components which are useful as diagnostic or chemical reagents and in the preparation of vaccines requires large scale cultivation of the microorganism.
Bordetella pertussis is a fastidious organism which has proved difficult to grow in large fermentors. Current methods for the culture of B. pertussis employ cultivation in stationary culture or in fermentors. Growth in stationary culture is labor intensive while cultivation on a fermentation scale requires vortex stirring and surface aeration. As a result, the effective volume of the fermentor is reduced and modification of the fermentor for growth of pertussis is often necessary, for example the baffles must be removed. Furthermore, the quantities of pertussis toxin produced during fermentation under these conditions are variable and often low.